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Integrins: Friends or Foes of Antitumor Cytotoxic T Lymphocyte Response

  • Chapter
Resistance of Cancer Cells to CTL-Mediated Immunotherapy

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT,volume 7))

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Abstract

Elimination of cancer cells by the immune system requires the induction of a strong and durable antitumor cytotoxic T lymphocyte (CTL) response. Immunotherapy approaches aim at generating tumor-specific CTL capable of migrating to the tumor site and at optimizing their functional activities toward target cells. Unfortunately, clinical trials indicate that despite an increase in the frequency and reactivity of antitumor CD8+ T lymphocytes, the efficacy of current immunotherapeutic strategies remains limited and rarely resulted in the eradication of malignant cells. Integrins and their ligands play critical roles in regulating T-cell effector functions, including adhesion to antigen presenting cells (APC), costimulation, migration to lymphoid organs and inflammatory sites, and extravasation. Although some of those are known to promote tumor cell proliferation and dissemination, others are required for T-lymphocyte homing and retention within the tumor microenvironment and for CTL activation and triggering of cytotoxic activity within a hostile ecosystem. In this chapter, we will briefly summarize findings involving integrins, in particular CD103 (αE/β7) and LFA-1 (αL/β2), and their respective ligands, E-cadherin and intercellular adhesion molecule 1 (ICAM-1), in regulating the effector phase of the antitumor T-cell response and we provide insights into the potential implication of their altered expression in tumor resistance to CTL-mediated cancer immunotherapy. The characterization of integrin-dependent pathways involved in the potentiation of antitumor CTL functions may lead to enhanced immune protection and improved cancer immunotherapy.

No conflict statement: No potential conflicts of interest were disclosed.

An erratum to this chapter is available at http://dx.doi.org/10.1007/978-3-319-17807-3_15

An erratum to this chapter can be found at http://dx.doi.org/10.1007/978-3-319-17807-3_15

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Abbreviations

APC:

Antigen-presenting cell

CAF:

Cancer-associated fibroblasts

ECM:

Extracellular matrix

EMT:

Epithelial-to-mesenchymal-transition

ICAM:

Intercellular adhesion molecule

IS:

Immune synapse

LFA:

Leukocyte function-associated antigen

mAb:

Monoclonal antibody

MTOC:

Microtubule-organizing center

pMHC-I:

Peptide-major histocompatibility complex class I

TAA:

Tumor-associated antigen

TCR:

T-cell receptor

TGF:

Transforming growth factor.

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Acknowledgements

This work was supported by grants from the INSERM, the Institut National du Cancer (INCa), the Ligue contre le Cancer and the Fondation pour la Recherche Médicale (FRM).

MB is supported by a grant from Gustave Roussy (SIRIC SOCRATE) and SC is supported by a grant from the FRM.

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Authors and Affiliations

  1. INSERM (Institut national de la Santé et de la Recherche médicale) Unité U753, Team 1: Tumor Antigens and T-Cell Reactivity, Villejuif, 94805, France

    Marie Boutet, Stephanie Cognac & Fathia Mami-Chouaib

  2. Gustave Roussy (Institut de Cancérologie Gustave Roussy), Gustave Roussy. 114, rue Édouard Vaillant, Villejuif, 94805, France

    Marie Boutet, Stephanie Cognac & Fathia Mami-Chouaib

  3. Université Paris-Sud, Orsay, 91400, France

    Marie Boutet, Stephanie Cognac & Fathia Mami-Chouaib

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  1. Marie Boutet
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  2. Stephanie Cognac
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  3. Fathia Mami-Chouaib
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Correspondence to Fathia Mami-Chouaib .

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Editors and Affiliations

  1. Department of Microbiology, Immunology a, University of California at Los Angeles,, Los Angeles, California, USA

    Benjamin Bonavida

  2. Institut Gustave Roussy, Villejuif, France

    Salem Chouaib

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Boutet, M., Cognac, S., Mami-Chouaib, F. (2015). Integrins: Friends or Foes of Antitumor Cytotoxic T Lymphocyte Response. In: Bonavida, B., Chouaib, S. (eds) Resistance of Cancer Cells to CTL-Mediated Immunotherapy. Resistance to Targeted Anti-Cancer Therapeutics, vol 7. Springer, Cham. https://doi.org/10.1007/978-3-319-17807-3_4

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